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Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
Social jetlag (SJ) occurs when sleep-timing irregularities from social or occupational demands conflict with endogenous sleep–wake rhythms. SJ is associated with evening chronotype and poor mental health, but mechanisms supporting this link remain unknown. Impaired ability to retrieve extinction memory is an emotion regulatory deficit observed in some psychiatric illnesses. Thus, SJ-dependent extinction memory deficits may provide a mechanism for poor mental health. To test this, healthy male college students completed 7–9 nights of actigraphy, sleep questionnaires, and a fear conditioning and extinction protocol. As expected, greater SJ, but not total sleep time discrepancy, was associated with poorer extinction memory. Unexpectedly, greater SJ was associated with a tendency toward morning rather than evening chronotype. These findings suggest that deficient extinction memory represents a potential mechanism linking SJ to psychopathology and that SJ is particularly problematic for college students with a greater tendency toward a morning chronotype.
OBJECTIVES/GOALS: The extent that Clinical and Translational Science Award (CTSA) programs offer resources accessible online for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged CEnR resources accessible online from CTSAs and mapped resources to CEnR core competencies. METHODS/STUDY POPULATION: Eight domains of CEnR core competencies were identified: knowledge/perceptions of CEnR; personal traits necessary for CEnR; knowledge of/relationships with communities; training for performing CEnR; CEnR methods; program evaluation; resource sharing and communication; and dissemination and advocacy. A systematic review of CEnR resources accessible online from CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for inclusion of each domain of CEnR core competencies. Domain scores across all resources and inter-rater reliability in scoring domains were assessed using descriptive statistics and Cohen’s kappa coefficients. RESULTS/ANTICIPATED RESULTS: Overall, 214 resources available from 24 CTSAs were eligible for full review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. “CEnR methods” (50.5%; 108 of 214) and “Knowledge of/relationships with the community” (40.2%; 86 of 214) were most frequently addressed and “Program evaluation” (12.1%; 26 of 214) and “Dissemination and advocacy” (11.2%; 24 of 214) were least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings guide CEnR stakeholders to identify CEnR resources accessible online and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competencies is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability. CONFLICT OF INTEREST DESCRIPTION: In addition to the funding information listed previously (see above), within the last three years, R.J. Piasecki has been employed as: Project Coordinator, CEnR Online Learning Project, Johns Hopkins University School of Nursing (Current) Temporary Employee (Doctoral Student Intern), Michigan State University Institute for Health Policy (Current) Clinical RN, Intrastaff at the Johns Hopkins Health System (Past) Research Data Analysis Assistant, Maryland Institute for Emergency Medical Services (Past - contracted)
In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
The National Cryo-Electron Microscopy Facility (NCEF) at the National Cancer Institute was launched in May of 2017 to provide free and rapid access to high-resolution cryo-EM data collection to United States researchers working on problems of broad general relevance to cancer biology. The decision about suitability of projects for data collection is made on a first-come, first-served basis by NCEF staff and is based solely on the quality of the screening images provided, without need for a scientific proposal. Here we provide an overview of the operation of the facility, typical data collection procedures, and some insights that have emerged from the structures reported from data collected at the facility.
One major challenge in the study of late-Quaternary extinctions (LQEs) is providing better estimates of past megafauna abundance. To show how megaherbivore population size varied before and after the last extinctions in interior Alaska, we use both a database of radiocarbon-dated bone remains (spanning 25–0 ka) and spores of the obligate dung fungus, Sporormiella, recovered from radiocarbon-dated lake-sediment cores (spanning 17–0 ka). Bone fossils show that the last stage of LQEs in the region occurred at about 13 ka ago, but the number of megaherbivore bones remains high into the Holocene. Sporormiella abundance also remains high into the Holocene and does not decrease with major vegetation changes recorded by arboreal pollen percentages. At two sites, the interpretation of Sporormiella was enhanced by additional dung fungal spore types (e.g., Sordaria). In contrast to many sites where the last stage of LQEs is marked by a sharp decline in Sporormiella abundance, in interior Alaska our results indicate the continuance of megaherbivore abundance, albeit with a major taxonomic turnover (including Mammuthus and Equus extinction) from predominantly grazing to browsing dietary guilds. This new and robust evidence implies that regional LQEs were not systematically associated with crashes of overall megaherbivore abundance.
Dietary fibre fermentation in humans and monogastric animals is considered to occur in the hindgut, but it may also occur in the lower small intestine. This study aimed to compare ileal and hindgut fermentation in the growing pig fed a human-type diet using a combined in vivo/in vitro methodology. Five pigs (23 (sd 1·6) kg body weight) were fed a human-type diet. On day 15, pigs were euthanised. Digesta from terminal jejunum and terminal ileum were collected as substrates for fermentation. Ileal and caecal digesta were collected for preparing microbial inocula. Terminal jejunal digesta were fermented in vitro with a pooled ileal digesta inoculum for 2 h, whereas terminal ileal digesta were fermented in vitro with a pooled caecal digesta inoculum for 24 h. The ileal organic matter fermentability (28 %) was not different from hindgut fermentation (35 %). However, the organic matter fermented was 66 % greater for ileal fermentation than hindgut fermentation (P = 0·04). Total numbers of bacteria in ileal and caecal digesta did not differ (P = 0·09). Differences (P < 0·05) were observed in the taxonomic composition. For instance, ileal digesta contained 32-fold greater number of the genus Enterococcus, whereas caecal digesta had a 227-fold greater number of the genus Ruminococcus. Acetate synthesis and iso-valerate synthesis were greater (P < 0·05) for ileal fermentation than hindgut fermentation, but propionate, butyrate and valerate synthesis was lower. SCFA were absorbed in the gastrointestinal tract location where they were synthesised. In conclusion, a quantitatively important degree of fermentation occurs in the ileum of the growing pig fed a human-type diet.
This project will work closely with existing service partners involved in street level services and focus on testing and evaluating three approaches for street level interventions for youth who are homeless and who have severe or moderate mentally illness. Youth will be asked to choose their preferred service approach:
Housing First related initiatives focused on interventions designed to move youth to appropriate and available housing and ongoing housing supports.
Treatment First initiatives to provide Mental Health/Addiction supports and treatment solutions, and; Simultaneous attention to both Housing and Treatment Together
Our primary objective is to understand the service delivery preferences of homeless youth and understand the outcomes of these choices. Our research questions include:
1. Which approaches to service are chosen by youth?
2. What are the differences and similarities between groups choosing each approach?
3. What are the critical ingredients needed to effectively implement services for homeless youth from the perspectives of youth, families and service providers?
Focus groups with staff and family members will occur to assist in understanding the nature of each of service approach, changes that evolve within services, & facilitators and barriers to service delivery. This work will be important in determining which approach is chosen by youth and why. Evaluating the outcomes with each choice will provide valuable information about outcomes for the service options chosen by youth. This assist in better identifying weaknesses in the services offered and inform further development of treatment options that youth will accept.
Effectiveness of medication treatment is determined by three components: treatment efficacy (symptom reduction), tolerability/safety, and adherence. Compared with efficacy and safety, research into adherence has been lacking. Nevertheless, medication non-adherence is a risk factor for relapse and for aggressive behavior in association with substance abuse in schizophrenia patients. Non-adherence has been estimated to cause approximately 40% of relapses in patients with schizophrenia. High rates of treatment discontinuation in all arms of the CATIE study illustrate the widespread nature of non-adherence. Most of previous research has defined non-adherence as a complete discontinuation of medication. However, many schizophrenia patients show partial adherence: they do not completely discontinue their medication, but they do not take all that has been prescribed. Partial adherence is more difficult to define and study than complete non-adherence.
e had the opportunity to study partial adherence in the context of a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10mg/d, 20 mg/d and 40 mg/d for patients with schizophrenia or schizoaffective disorder (N=599). Medication non-adherence was measured by pill counts. Baseline characteristics including demographics, illness history and symptom severity were investigated as potential risk factors for treatment non-adherence.
Results and conclusion
Approximately 1/3 of patients were non-adherent with their medication at least once during the 8-week study. These non-adherent patients had significantly less improvement compared to adherent patients. Adherent patients had greater weight gain than the non-adherent ones. Among the available baseline measures, greater baseline depression severity appeared to be a significant risk factor for non-adherence.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Surgical site infections (SSIs) are among the most common healthcare-associated infections in low- and middle-income countries. To encourage establishment of actionable and standardized SSI surveillance in these countries, we propose simplified surveillance case definitions. Here, we use NHSN reports to explore concordance of these simplified definitions to NHSN as ‘reference standard.’
When Russians penetrated Siberia in the late sixteenth century they found most of the area inhabited by reindeer herders or nomadic pastoralists speaking Uralic, Turkic, Mongolic, and Tungusic languages. Western Siberia contained Khanty (Ostyak) and Mansi (Vogul) dialects belonging to the Ugrian subgroup of Uralic. Across the northeast were Nenets, Enets, and Nganasan tribes speaking Uralic languages of the Samoyedic branch.
Mycoprotein is a food high in both dietary fibre and non-animal-derived protein. Global mycoprotein consumption is increasing, although its effect on human health has not yet been systematically reviewed. This study aims to systematically review the effects of mycoprotein on glycaemic control and energy intake in humans. A literature search of randomised controlled trials was performed in PubMed, Embase, Web of Science, Google Scholar and hand search. A total of twenty-one studies were identified of which only five studies, totalling 122 participants, met the inclusion criteria. All five studies were acute studies of which one reported outcomes on glycaemia and insulinaemia, two reported on energy intake and two reported on all of these outcomes. Data were extracted, and risk-of-bias assessment was then conducted. The results did not show a clear effect of acute mycoprotein on blood glucose levels, but it showed a decrease in insulin levels. Acute mycoprotein intake also showed to decrease energy intake at an ad libitum meal and post-24 h in healthy lean, overweight and obese humans. In conclusion, the acute ingestion of mycoprotein reduces energy intake and insulinaemia, whereas its impact on glycaemia is currently unclear. However, evidence comes from a very limited number of heterogeneous studies. Further well-controlled studies are needed to elucidate the short- and long-term effects of mycoprotein intake on glycaemic control and energy intake, as well as the mechanisms underpinning these effects.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Interactions between polyphenols and non-digestible carbohydrates (NDC) can impact on polyphenolic metabolites bioavailability, including phenolic acids. The BLEND2 trial (NCT03840746) aims to study longer-term interactions of a flavonoid-rich food with/without NDC on microbiota metabolites and cardiometabolic markers. Trial feasibility using a bespoke food was tested.
Material and Methods
The soup was developed locally containing cherry tomatoes, tomato puree, red onion, fresh lovage, with/without the NDC inulin (10g), but improved and processed with Campden BRI, Chipping Campden, UK. The final product (~400g/ tin) was evaluated with VAS scales (0–10) for appearance, smell, taste and overall palatability, and flavonoid content evaluated using liquid chromatography-mass spectrometry. The 3-arm parallel randomised blinded design (control soup, soup + inulin, habitual diet control) recruited self-reported healthy participants (BMI > 25, 40–70y) with urine, blood, faecal samples collected at baseline, 3-week, 6-weeks.
Both soups scored similarly (n = 8 testers) for visual appeal (with inulin 5.1 ± 2.1; without 4.5 ± 2.0); smell (with 5.9 ± 1.7; without 5.4 ± 0.8); taste (with 6.6 ± 2.0; without 5.5 ± 2.3), aftertaste (with 6.3 ± 2.9; without 5.4 ± 2.3) and overall palatability (with 7.0 ± 1.9; without 6.1 ± 2.1).
The soups (A&B), 1 tin/day, provide 68.5 ± 10.9 mg total flavonoids (soup A n = 3, quercetin equivalents) and 74.0 ± 16.1 mg (soup B, n = 3): quercetin (A 1.2 ± 0.1 mg; B 1.3 ± 0.6 mg), quercetin-4-glucoside (A 3.9 ± 1.0 mg; B 4.1 ± 1.9 mg), quercetin-3-rutinoside (A 23.0 ± 3.2 mg; B 20.5 ± 1.0 mg), quercetin 3,4-diglucosides (A 40.5 ± 6.9 mg; B 48.2 ± 14.9 mg).
Following notes of interest (n = 415), n = 111 attended screening, n = 34 did not proceed (medications, opt-out; 31%). Participants (n = 77) are mostly British (79%), median age 56y (IQR 49-62) with a median BMI of 31 (IQR 28-35). Dropout was low (12%) and early in the study (personal issues, n = 2; gastrointestinal issues, n = 2; failure to comply with protocol, n = 2; acid reflux symptoms, n = 1; dislike of test food, n = 1). Adverse events included acid reflux/heartburn (n = 4), gastrointestinal distress (n = 3) accounting for 3 drop-outs.
To date, urine, blood and faecal samples (study day or day + 1) were collected at all timepoints, for all participants. Participation (soup arms) has not led to body weight or blood lipids changes compared to control group.
The protocol for this 6-week trial has proved feasible with lower dropout than expected. Soup flavonoid content representing ~16% of average European flavonoid intakes, with inulin (10g) half the UK daily fibre intake. The soup was well accepted with few reports of adverse issues. Recruitment in this population is challenging, due to high levels of medication and ill health.